دورية أكاديمية
4-Octyl itaconate protects chondrocytes against IL-1β-induced oxidative stress and ferroptosis by inhibiting GPX4 methylation in osteoarthritis.
| العنوان: | 4-Octyl itaconate protects chondrocytes against IL-1β-induced oxidative stress and ferroptosis by inhibiting GPX4 methylation in osteoarthritis. |
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| المؤلفون: | Pan X; Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China., Kong X; Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China., Feng Z; Sir Run Run Shaw Hospital, Hangzhou 310000, China., Jin Z; Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China., Wang M; Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China. Electronic address: dolphin123x@163.com., Lu H; Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China. Electronic address: 13758076161@163.com., Chen G; Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China. Electronic address: jxeylhg@163.com. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112531. Date of Electronic Publication: 2024 Jun 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Chondrocytes*/drug effects , Chondrocytes*/metabolism , Ferroptosis*/drug effects , Oxidative Stress*/drug effects , Succinates*/pharmacology , Succinates*/therapeutic use , Interleukin-1beta*/metabolism , Osteoarthritis*/drug therapy , Phospholipid Hydroperoxide Glutathione Peroxidase*/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase*/genetics , Mice, Inbred C57BL*, Animals ; Mice ; Male ; Humans ; Methylation/drug effects ; Reactive Oxygen Species/metabolism ; Cells, Cultured ; Disease Models, Animal |
| مستخلص: | The role of oxidative stress and ferroptosis in osteoarthritis (OA) pathogenesis is increasingly recognized. Notably, 4-octyl Itaconate (OI) has been documented to counteract oxidative stress and inflammatory responses, highlighting its therapeutic potential in OA. This study explored the effects of OI on GPX4 methylation, oxidative stress, and ferroptosis in chondrocytes affected by OA. Our results demonstrated that OI mitigated IL-1β-induced chondrocyte degeneration in a dose-dependent manner. It also suppressed reactive oxygen species (ROS) production and sustained GPX4 expression, thereby attenuating the degenerative impact of IL-1β and Erastin on chondrocytes by curtailing ferroptosis. Moreover, we observed that blocking GPX4 methylation could alleviate IL-1β-induced degeneration, oxidative stress, and ferroptosis in chondrocytes. The regulatory mechanism of OI on GPX4 expression in chondrocytes involved the inhibition of GPX4 methylation. In a mouse model of OA, OI's protective effects against OA were comparable to those of Ferrostatin-1. Thus, OI reduced chondrocyte degeneration, oxidative stress, and ferroptosis by inhibiting GPX4 methylation, offering a novel mechanistic insight into its therapeutic application in OA. (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: 4-Octyl itaconate; Ferroptosis; GPX4; Methylation; Osteoarthritis |
| المشرفين على المادة: | 0 (Succinates) 0 (Interleukin-1beta) EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase) 0 (4-octyl itaconate) 0 (Reactive Oxygen Species) EC 1.11.1.9 (glutathione peroxidase 4, mouse) |
| تواريخ الأحداث: | Date Created: 20240621 Date Completed: 20240710 Latest Revision: 20240805 |
| رمز التحديث: | 20240805 |
| DOI: | 10.1016/j.intimp.2024.112531 |
| PMID: | 38906009 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2024.112531 |